Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Language: Английский

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Osteoarthritis: pathogenic signaling pathways and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 3, 2023

Abstract Osteoarthritis (OA) is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide. OA was believed be caused by the wearing tearing of articular cartilage, but it now commonly referred as whole-joint initiated with biochemical cellular alterations in synovial tissues, which histological structural changes ends up whole tissue dysfunction. Currently, there no cure for OA, partly due lack comprehensive understanding pathological mechanism initiation progression disease. Therefore, better signaling pathways key molecules involved pathogenesis crucial therapeutic target design drug development. In this review, we first summarize epidemiology including its prevalence, incidence burdens, risk factors. We then focus on roles regulation pathways, such Wnt/β-catenin, NF-κB, focal adhesion, HIFs, TGFβ/ΒΜP FGF regulators AMPK, mTOR, RUNX2 onset development OA. addition, factors associated MMPs, ADAMTS/ADAMs, PRG4, are discussed detail. Finally, provide updates current clinical therapies trials biological treatments drugs Research advances basic knowledge cartilage biology will have significant impact translational value developing strategies.

Language: Английский

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D‐mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF‐2α‐dependent manner

Cell Proliferation, Journal Year: 2021, Volume and Issue: 54(11)

Published: Sept. 25, 2021

Abstract Objectives Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D‐mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether interferes chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. Materials methods In vivo anterior cruciate ligament transection (ACLT)‐induced OA mouse model an vitro study of chondrocytes microenvironment induced by interleukin‐1β (IL‐1β) exposure were employed. Combined with Epas1 gene gain‐ loss‐of‐function, histology, immunofluorescence, quantitative RT‐PCR, Western blot, viability flow cytometry experiments performed evaluate the chondroprotective effects progression role hypoxia‐inducible factor 2 alpha (HIF‐2 α) D‐mannose‐induced resistance chondrocytes. Results exerted a effect attenuating sensitivity alleviated progression. HIF‐2α was identified as central mediator Furthermore, overexpression Ad‐ intra‐articular injection abolished eliminated suppressor. Conclusions alleviates suppressing HIF‐2α‐mediated ferroptosis, indicating be potential strategy for ferroptosis‐related diseases.

Language: Английский

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Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues

Bone Research, Journal Year: 2021, Volume and Issue: 9(1)

Published: Oct. 20, 2021

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond physical signals from both the external internal environments. The mechanotransduction process requires range of special proteins termed mechanotransducers convert mechanical forces into biochemical in cells. Piezo are mechanically activated nonselective cation channels largest plasma membrane ion reported thus far. regulation two family members, Piezo1 Piezo2, has been have essential functions mechanosensation transduction different organs tissues. Recently, predominant contributions were occur skeletal system, especially bone development mechano-stimulated homeostasis. Here we review current studies focused on tissue-specific Piezo2 various backgrounds with highlights their importance regulating cell mechanotransduction. In this review, emphasize diverse related signaling pathways osteoblast lineage cells chondrocytes. We also summarize our understanding channel structures key findings about PIEZO gene mutations human diseases.

Language: Английский

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An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 31, 2023

Abstract Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development a biofunctional hydrogel improved delivery required. In this study, we introduce liposome-anchored teriparatide (PTH (1–34)) incorporated into gallic acid-grafted gelatin injectable (GLP hydrogel). We show that GLP can form in situ and without affecting knee motion after intra-articular mice. demonstrate controlled, sustained release PTH (1–34) from hydrogel. find promotes ATDC5 cell proliferation protects IL-1β-induced cells further OA progression regulating PI3K/AKT signaling pathway. Further, hydrogels OA-induced mouse model glycosaminoglycans synthesis cartilage degradation, supporting potential biomaterial treatment.

Language: Английский

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Exercise induced meteorin-like protects chondrocytes against inflammation and pyroptosis in osteoarthritis by inhibiting PI3K/Akt/NF-κB and NLRP3/caspase-1/GSDMD signaling

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 158, P. 114118 - 114118

Published: Dec. 15, 2022

The production of metrnl, a novel adipomyokine, is induced upon exercise in adipose tissue and skeletal muscle. In this study, we investigated the anti-inflammatory antipyroptotic effects exercise-induced metrnl producted rats vitro vivo. Forty Sprague-Dawley were divided randomly into five groups: control (CG), osteoarthritis (OA) with sedentary lifestyle (OAG), OA low intensity (OAL), moderate (OAM), high (OAH). correlation between level degree was detected using ELISA, X-ray imaging, histology, immunohistochemistry Primary chondrocytes preincubated recombinant before interleukin-1β administration to verify metrnl. Western blotting quantitative reverse transcription (qRT)-PCR used evaluate differences protein mRNA expression groups, respectively. Reactive oxygen species (ROS) assay, immunofluorescence, transmission electron microscopy (TEM), flow cytometry morphological changes pyroptosis chondrocytes. moderate-intensity treadmill group, severity showed maximum relief levels had most significant increase. Metrnl exerted its effect through suppression PI3K/Akt/NF-κB pathway IL-1β-induced chondrocytes, which accompanied recovery collagen II attenuation MMP13 ADAMTS5. Moreover, ameliorated chondrocyte by inhibiting activation nod-like receptor protein-3/caspase-1/gasdermin D cascade. conclusion, improves inflammation increasing release, inhibits further NLRP3/caspase-1/GSDMD signaling pathways.

Language: Английский

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Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage

Drug Delivery, Journal Year: 2022, Volume and Issue: 29(1), P. 767 - 791

Published: March 9, 2022

Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for may be an attractive strategy prevent rapid clearance and improve half-life at joint cavity. Such will therapeutic effects anti-inflammatory in Whereas, disease-modifying drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), cartilage-permeable DDSs required maximize their efficacy. This review provides overview structure healthy pathological conditions, introduces advances permeable DDSs, discusses rational design treatment. We hope ideas generated this promote effective future.

Language: Английский

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Roles of focal adhesion proteins in skeleton and diseases

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(3), P. 998 - 1013

Published: Oct. 3, 2022

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support movement, protection internal organs, production blood cells regulation calcium phosphate metabolism. prevalence diseases disorders, such as osteoporosis bone fracture, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, increases with age, causing pain loss mobility creating huge social economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that composed the extracellular matrix (ECM), integrins, intracellular cytoskeleton proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) integrin-linked protein (ILK) proteins. FA acts mechanical linkage connecting ECM key role mediating cell-environment communications modulates important processes, cell attachment, spreading, migration, differentiation mechanotransduction, different system by impacting distinct outside-in inside-out signaling pathways. This review aims to integrate up-to-date knowledge proteins health disease focuses on specific molecular mechanisms underlying therapeutic targets for diseases.

Language: Английский

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Trimanganese Tetroxide Nanozyme protects Cartilage against Degeneration by Reducing Oxidative Stress in Osteoarthritis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(17)

Published: April 23, 2023

Osteoarthritis, a chronic degenerative cartilage disease, is the leading cause of movement disorders among humans. Although specific pathogenesis and associated mechanisms remain unclear, oxidative stress-induced metabolic imbalance in chondrocytes plays crucial role occurrence development osteoarthritis. In this study, trimanganese tetroxide (Mn

Language: Английский

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Obesity, Metabolic Syndrome, and Osteoarthritis—An Updated Review

Current Obesity Reports, Journal Year: 2023, Volume and Issue: 12(3), P. 308 - 331

Published: Aug. 14, 2023

Language: Английский

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